Is MAPK8 p.Gly16= (c.48A>G) pathogenic?

MAPK8 p.Gly16= (c.48A>G) is classified Likely benign in MAPK8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-27). Ultra-rare (popmax 0.0803%, sas); Associated with MAPK8-related disorder.

What condition is associated with MAPK8 p.Gly16= (c.48A>G)?

MAPK8 p.Gly16= (c.48A>G) is associated with MAPK8-related disorder (ClinVar).

How common is MAPK8 p.Gly16= (c.48A>G) in the general population?

MAPK8 p.Gly16= (c.48A>G) is ultra-rare (popmax 0.0803%, sas) (gnomAD).

MAPK8 p.Gly16=

c.48A>G · rs137900446 · VCV3042498

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0803%, sas)

Conditions

MAPK8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -2, phastCons 1
Overall
CADD	9.235	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0803% South Asian · 72/89,662 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.0138% 222/1,604,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.184%	544
South Asiangrpmax	0.0803%	1,245
Remaining individualsnot grpmax-eligible	0.0436%	2,296
Middle Eastern	0.0331%	3,023
Finnishnot grpmax-eligible	0.0219%	4,565
Admixed American	0.00518%	19,297
European (non-Finnish)	0.00425%	23,528

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MAPK8
Protein: p.Gly16=
Coding: c.48A>G
MANE Select: NM_001323329
dbSNP: rs137900446
Type: single nucleotide variant
Location: chr10:48401708 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 83.75 · 41 PDB

Full MAPK8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAPK8-related disorder

Similar variants

MAPK8 p.Phe170= Likely benign same condition
MAPK8 c.123-51A>C Benign ★★ same type
MAPK8 c.253-80T>A Benign ★★ same type
MAPK8 c.311+37A>G Benign ★★ same type
MAPK8 c.450+141T>G Benign ★★ same type
MAPK8 c.689-56T>A Benign ★★ same type
MAPK8 c.997-51T>A Benign ★★ same type
MAPK8 c.-49-77C>A Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mapk8-p-gly16 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown